Prevalence of alcohol and noninjection drug use is markedly high in select populations and there is concern that use of these substances accelerates the HIV epidemic. This review presents recent evidence on the epidemiology of alcohol and noninjection drug use and HIV risk among heterosexuals and men who have sex with men (MSM). This article also highlights recent data on syndemics, in which substance use is combined with other psychosocial issues to help fuel the HIV epidemic among MSM. Furthermore, the article presents recent evidence on the effects of substance use on HIV disease progression. Finally, recent data on HIV prevention among substance users are reviewed.
Alcohol use among heterosexuals in Africa
Alcohol use is the most common type of substance abuse in sub-Saharan Africa, a region severely devastated by the HIV epidemic [1•,2••]. Most alcohol consumption in southern Africa occurs in alcohol-serving establishments and drinking venues, which are also places for meeting sexual partners [2••]. In a study of shebeens , which are informal alcohol-serving venues in Cape Town, South Africa, 28% of men and women reported meeting one or more sexual partners at these localities. Compared with those who had not met a sexual partner at shebeens, participants who had met at least one partner were more likely to be problem drinkers, be male, have higher sexual outcome expectancies from alcohol use, have two or more sexual partners, and have more unprotected vaginal intercourse.
Recent evidence supports a strong association between alcohol use and HIV infection among heterosexuals in sub-Saharan Africa [4••], although it is unclear whether alcohol is the sole contributor to increased sexual risk behavior or whether other factors are involved in the alcohol and HIV-infection pathway. A meta-analysis of 20 studies, mostly cross-sectional, in eastern and southern Africa found that persons who drank alcohol were more likely to be HIV-infected than those who did not drink alcohol [pooled unadjusted odds ratio (OR) = 1.70, 95% confidence interval (CI) 1.45–1.99 from 20 studies; adjusted OR = 1.57, 95% CI 1.42–1.72 from 11 studies). The risk estimates were stable across sex, though high-risk groups, such as bar and hotel workers, had higher HIV risk than population-based samples [4••].
Stronger evidence for a direct link between alcohol use and HIV infection was found in two prospective studies in Uganda and Tanzania [4••]. In a longitudinal, population-based cohort in Uganda from 1994 to 2002, the HIV incidence rate ratio (IRR) was significantly elevated when either or both partners drank alcohol before sex (adjusted IRR = 1.62, 95% CI 1.15–2.29 among men and adjusted IRR = 1.62, 95% CI 1.19–2.20 among women), after adjusting for sociodemographic and sexual behavior characteristics . In a Tanzanian cohort of HIV-negative women attending family planning clinics between 1992 and 1995, women who drank alcohol were significantly more likely to acquire HIV than their nondrinking counterparts (relative risk = 1.85, 95% CI 1.14–3.00) .
Alcohol use has been linked to increased frequency of unprotected intercourse, increased number of sexual partners, and failure to apply condoms correctly [4••]. The Ugandan study  found that alcohol consumption was significantly related to inconsistent condom use, increased number of sexual partners, and extramarital relationships in the past year among both men and women.
The amount of alcohol drinking, rather than the frequency of drinking, has been shown to be a predictor of high-risk sexual behavior in southern Africa [2••]. Those who reported heavy alcohol consumption and being intoxicated during sexual activities were less likely to use condoms and more likely to have concurrent sexual partners. Although men were more likely to ingest alcohol and be involved in higher sexual risk behavior than women, women tended to drink in greater quantities than men. Furthermore, women were more likely to be involved in transactional sex in which their male sexual partners purchased alcoholic drinks for them in exchange for sex [2••].
Alcohol drinking has been associated with sexual violence, assault, and rape, which increase women's risk of acquiring HIV [4••]. In a community-based sample of young women aged 20–44 years in Tanzania, women who abused alcohol were more likely to report a history of sexual or physical violence [1•].
Alcohol drinking is also frequently seen among the HIV-infected. From daily diaries used to collect event-specific data to assess the temporal relationship of alcohol drinking to unprotected sexual events among 82 HIV-infected men and women, participants reported drinking an average of 6.13 alcoholic beverages when they drank and engaging in 4927 sexual events over 42 days. A majority (80%) of these sexual events were unprotected, of which more than half (58%) were with partners who were either HIV-negative or had unknown HIV status. Alcohol use before sex increased the proportion and number of ensuing unprotected sexual episodes, but only among those who were moderate or higher risk drinkers, based on amount of alcohol consumed. Among moderate or higher risk drinkers, an increase in the proportion and number of unprotected sexual intercourse was associated with greater number of alcoholic drinks before sex. The relationship between alcohol quantity and unprotected sex was more prominent when sex occurred with casual or secondary partners than with main or steady partners .
Substance use among men who have sex with men in developed countries
Substance-using MSM tend to use a wide variety of drugs [e.g., marijuana, cocaine, amyl nitrates (poppers), methamphetamines, hallucinogens, methylenedioxy-methamphetamine (MDMA, ecstasy), ketamine, γ-hydroxybutyrate (GHB)] and use them in combination or sequentially . In a study of 450 drug-using MSM and bisexual men in New York City, polydrug use was common, with high levels of association noted between use of methamphetamine, ecstasy, cocaine, ketamine, and GHB .
In a cross-sectional study of 214 MSM who utilized mobile van services, including HIV and other sexually transmitted infection (STI) testing, in Massachusetts, concurrent use of multiple drugs during sex was significantly associated with HIV infection and a history of one or more STIs. Compared with men who were nonpolydrug users, men who reported polydrug use were more likely to have a higher number of sexual partners, anonymous sexual partners, partners with whom they became acquainted for less than 12 h prior to having sex with them, and partners whom they met on the Internet. After adjusting for sociodemographic factors, HIV status, and history of STI and depression, polydrug use during sex was found to be significantly associated with unprotected anal intercourse .
Most drug use among MSM is sporadic and occurs in conjunction with attending social venues or with sexual activity rather than at the level of drug dependency [11,12]. Although most MSM (79–89%) report some recent alcohol use, only a minority (8–16%) report frequent and heavy alcohol use [12,13].
Although the association between substance use and HIV-infection risk has been well documented in the literature , recent studies have revealed specific associations, which can be utilized to better inform intervention development. A recent longitudinal study evaluating 4003 HIV-negative MSM in the Multicenter AIDS Cohort Study [15•] confirmed that methamphetamine use was significantly associated with HIV seroconversion (adjusted hazard ratio = 1.46, 95% CI 1.12–1.92). Additional factors associated with HIV infection included use of cocaine, ecstasy, and poppers, as well as higher number of sexual partners and higher number of unprotected receptive anal sexual partners. A multiplicative effect was seen among men who used both methamphetamines and poppers. Furthermore, when methamphetamine use was compared to number of unprotected receptive anal sexual partners, a dose–response relationship was seen with HIV seroconversion (joint relative hazard ratio = 2.7 for one partner, 7.8 for two to four partners, 13.6 for five and more partners).
In a retrospective case–control study of 444 recently HIV-infected and HIV-negative MSM in Chicago and Los Angeles, use of poppers, methamphetamines, sildenafil, ketamine, and GHB was significantly associated with unprotected anal intercourse in the 6 months prior to a positive HIV test result. In multivariate analysis, recent HIV infection was associated with sildenafil and popper use during unprotected anal intercourse, along with unprotected anal intercourse with an HIV-positive partner in the past 6 months . In a study of 503 ethnically and racially diverse MSM who attended public venues in New York City, amphetamine use was significantly associated with unprotected receptive anal intercourse with nonmain partners (OR = 2.35, 95% CI 1.05–5.25) . The association of specific drugs with sexual positioning was also seen in a study of 388 MSM in San Francisco. Examining event-specific comparisons, methamphetamine use was significantly associated with unprotected receptive anal sex (OR = 2.03, 95% CI 1.09–3.76), whereas sildenafil use was associated with unprotected insertive anal intercourse (OR = 6.51, 95% CI 2.46–17.24). The effects were more pronounced with sex with partners who were HIV-discordant or had unknown HIV status . These findings may be explained by the fact that methamphetamines, particularly when used at high doses, can lead to impotence, whereas sildenafil counteracts erectile dysfunction.
In a longitudinal study employing a community-based sample of active drug-using MSM and bisexual men in New York City , methamphetamine use was associated with unprotected insertive and receptive anal intercourse with casual partners who were HIV-infected or had unknown HIV status during a 1-year period. The relationship between methamphetamine use and unprotected anal intercourse was particularly marked for HIV-infected men.
In contrast to noninjection drug use, data on the association between alcohol use and high-risk sexual behavior among MSM are mixed [19••]. Three studies in particular (two prospective and one cross-sectional) have shown a positive and significant link between alcohol drinking, especially heavy, episodic drinking, and HIV infection. In contrast, the association between alcohol use as a global measurement and unprotected anal intercourse is equivocal. Situational association studies, in which alcohol drinking is assessed in sexual contexts, have generally demonstrated a significant association between situational alcohol consumption and unprotected anal intercourse among MSM. Event-level evidence for an association between alcohol use during a specific sexual episode and high-risk behavior is mixed [19••].
Substance use, mental health problems, and sexual risk behaviors commonly experienced by MSM often combine to amplify HIV-infection risk in this population in what is known as a syndemic effect . A syndemic appears to be present in young MSM, who are especially vulnerable to HIV infection. In a study evaluating baseline data from the EXPLORE Study [21•], young MSM were more likely to consume heavy alcohol, to use marijuana, hallucinogens, cocaine, and amphetamine, and to report depressive symptoms than older MSM. Yet young MSM were less likely to report using interventions, such as counseling and medications, for psychiatric problems. In a study of childhood sexual abuse, substance use, and HIV-infection risk among adult MSM in four US cities, depressive symptoms, suicidal ideation, recent substance use (including alcohol, methamphetamines, marijuana, crack cocaine, and ecstasy), and sexual risk behaviors were more frequently reported among men who had forced sex experiences during childhood .
Substance use among men who have sex with men in developing countries
Limited published data are available on the epidemiology of substance use among MSM in developing countries. A recent study among HIV-infected MSM attending an STI clinic in Lima, Peru  showed that substance use prior to sex was common; however, substance use was not found to be significantly associated with recent unprotected anal intercourse. In Brazil, recent drug use, including marijuana, crack cocaine, amphetamines, and ecstasy, was significantly higher among MSM sex workers than among the general MSM population (56 vs. 27%, respectively) .
Limited studies to date have explored the relationship between alcohol and other substance use and HIV risk among MSM in sub-Saharan Africa. In a study of MSM living in South African townships, alcohol was the most common form of substance use, reported in 78% of the participants. Marijuana was the second most frequently used drug (29%), whereas use of other substances, including methaqualone, heroin, methamphetamines, ecstasy, and methcathinone, was reported by less than 5% of the participants. Adjusting for age and sexual risk behavior, men who drank alcohol at least once per week and were drunk less than once per week were 4.1 times more likely to have unprotected anal intercourse compared with men who drank alcohol less than once per week, whereas men who drank regularly and drank to intoxication at least once per week were 2.6 times more likely to report unprotected anal intercourse . In a qualitative study of 78 drug-using MSM in three cities in South Africa, frequently used drugs included crack cocaine, heroin, cannabis, cocaine powder, ecstasy, methamphetamines, methaqualone, and methcathinone, with the first three drugs being the most popular. The drugs were often used in the context of sexual intercourse, either before, during or after sex. Drug use often influenced high-risk sexual behavior, including failing to use condoms during sex, having sex with strangers, partaking in group sex, having multiple sexual partners, having prolonged sexual encounters, and having sex in exchange for drugs or money to purchase drugs .
Substance use and HIV disease progression
Substance use is prevalent among HIV-infected individuals with several implications. It has been associated with increased HIV-transmission risk behavior, inadequate adherence to antiretroviral therapy, and subsequent emergence of drug resistance. Antiretroviral adherence is generally lower among drug-using HIV-infected persons, especially during drug binges. Poor adherence or complete cessation of antiretroviral medications during these intervals can lead to the development of HIV-drug resistance and treatment failure . In a study of self-reported antiretroviral therapy adherence among 247 HIV-infected adults, poor adherence was significantly associated with alcohol consumption of five or more drinks per occasion (P = 0.008) and use of amphetamines or ecstasy in the past month (P = 0.01). Those with poor medication adherence also had higher perceived stress level and depression score .
Another analysis of 1086 HIV-infected women showed that women using cocaine or heroin were less likely to make HIV primary care (OR = 0.67, 95% CI 0.61–0.73) and gynecologic clinic appointments (OR = 0.57, 95% CI 0.45–0.71) .
To date, there is inconclusive evidence that substance use directly affects HIV disease progression . Recent data have shown that methamphetamines elevate cytokine levels and may be involved in immune activation in chronically HIV-infected individuals. Methamphetamine use has been associated with higher plasma HIV viral load and lower antiretroviral therapy efficacy . Large epidemiologic studies of HIV-positive persons in the United States and Europe, however, have provided mixed results on the association between substance use and HIV disease progression, suggesting the involvement of mediating factors such as antiretroviral therapy adherence and access, comorbidities, and viral strain .
In a recent study, crack cocaine use was found to be a strong predictor of HIV disease progression among women. Among 1686 HIV-infected women enrolled in the multisite Women's Interagency HIV Study cohort, persistent crack users were 3.61 times more likely to die from AIDS-related causes than noncrack users, after controlling for sociodemographic factors, antiretroviral therapy adherence, alcohol use, HIV-infection duration, and baseline virological and immunological parameters. Persistent and intermittent crack users had lower CD4 T cell and higher HIV viral load counts than nonusers and were more likely to develop new AIDS-defining diseases [30•].
HIV prevention among substance users
Efforts to reduce alcohol and substance use can have a substantial impact on lowering HIV risk behaviors and thus, HIV-infection rates [4••]. A pilot behavioral intervention study was conducted in drug using South African women, who were randomized to either individual or group-based intervention. At 1-month follow-up after the intervention, significant reductions in sexual risk behaviors, including decreased frequency of alcohol and drugs before or during sex, were found in both intervention groups, with no differences noted between the two groups .
A limited number of intervention trials among substance-using MSM have been conducted. Contingency management is a behavioral intervention that provides positive reinforcements, including vouchers for goods or services, for a desired behavior, such as methamphetamine abstinence, which has been shown to be effective in reducing substance use among MSM [32,33].
A large intervention trial among 983 methamphetamine-using young adults between 18 and 25 years of age in Chiang Mai, Thailand compared a peer network intervention with standard life-skills education in lowering drug use, sexual risk behavior, and incident STI during a 12-month follow-up period. Substantial decrease in methamphetamine use and increase in condom use were found in both intervention arms, with no marked differences between the groups .
Because substance use is an important, and potentially modifiable, risk factor for HIV infection, complete integration of routine screening and prevention efforts for substance use into HIV prevention efforts is needed. Prevention efforts should target groups that are most likely to experience substance use problems, specifically frequent, heavy, and problem alcohol drinkers among heterosexuals in sub-Saharan Africa, MSM in the developed and developing countries, and drug-using HIV-infected individuals who are at high risk of transmitting HIV. More research is needed to develop effective interventions for these critical populations.
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Additional references related to this topic can also be found in the Current World Literature section in this issue (pp. 340–341).
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